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使用猪颈动脉制备肝素化和肝细胞生长因子涂层的去细胞支架。

Development of heparinized and hepatocyte growth factor-coated acellular scaffolds using porcine carotid arteries.

机构信息

Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, People's Republic of China.

出版信息

J Biomed Mater Res B Appl Biomater. 2024 Jan;112(1):e35317. doi: 10.1002/jbm.b.35317. Epub 2023 Aug 16.

Abstract

Tissue-engineered blood vessel substitutes have been developed due to the lack of suitable small-diameter vascular grafts. Xenogeneic extracellular matrix (ECM) scaffolds have the potential to provide an ideal source for off-the-shelf vascular grafts. In this study, porcine carotid arteries were used to develop ECM scaffolds by decellularization and coating with heparin and hepatocyte growth factor (HGF). After decellularization, cellular and nucleic materials were successfully removed with preservation of the main compositions (collagen, elastin, and basement membrane) of the native ECM. The ultimate tensile strength, suture strength, and burst pressure were significantly increased after cross-linking. Pore size distribution analysis revealed a porous structure within ECM scaffolds with a high distribution of pores larger than 10 μm. Heparinized scaffolds exhibited sustained release of heparin in vitro and showed potent anticoagulant activity by prolonging activated partial thromboplastin time. The scaffolds showed an enhanced HGF binding capacity as well as a constant release of HGF as a result of heparin modification. When implanted subcutaneously in rats, the modified scaffolds revealed good biocompatibility with enzyme degradation resistance, mitigated immune response, and anti-calcification. In conclusion, heparinized and HGF-coated acellular porcine carotid arteries may be a promising biological scaffold for tissue-engineered vascular grafts.

摘要

由于缺乏合适的小直径血管移植物,人们已经开发出了组织工程血管替代物。异种细胞外基质(ECM)支架具有为现成的血管移植物提供理想来源的潜力。在这项研究中,使用猪颈动脉通过脱细胞和肝素及肝细胞生长因子(HGF)包被来开发 ECM 支架。脱细胞后,通过保留天然 ECM 的主要成分(胶原、弹性蛋白和基底膜),成功去除了细胞和核酸物质。交联后,最终拉伸强度、缝合强度和爆裂压力显著增加。孔隙率分布分析显示 ECM 支架内存在多孔结构,其中大于 10 μm 的孔分布较高。肝素化支架在体外表现出肝素的持续释放,并通过延长激活部分凝血活酶时间表现出强大的抗凝活性。由于肝素修饰,支架显示出增强的 HGF 结合能力和 HGF 的持续释放。当植入大鼠皮下时,改性支架表现出良好的生物相容性,具有抗酶降解、减轻免疫反应和抗钙化的能力。总之,肝素化和 HGF 包被的脱细胞猪颈动脉可能是组织工程血管移植物有前途的生物支架。

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